The role of extracellular vesicle fusion with target cells in triggering systemic inflammation
(2024) In Nature Communications 15.- Abstract
Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally... (More)
Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.
(Less)
- author
- organization
-
- Host parasite interactions (research group)
- Infection Medicine (BMC)
- Respiratory Medicine and Allergology Research Group (research group)
- Respiratory Medicine, Allergology, and Palliative Medicine
- LUCC: Lund University Cancer Centre
- Surgery (research group)
- Translational infection medicine (research group)
- epIgG (research group)
- Breast/lung cancer (research group)
- Division of Translational Cancer Research
- Breast and Ovarian Cancer Genomics (research group)
- Breast/lungcancer
- Clinical Sciences, Helsingborg
- EpiHealth: Epidemiology for Health
- publishing date
- 2024-02-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Mice, NF-kappa B/metabolism, Extracellular Vesicles/metabolism, Biological Transport, Signal Transduction, Inflammation/pathology
- in
- Nature Communications
- volume
- 15
- article number
- 1150
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85184724486
- pmid:38326335
- pmid:38326335
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-024-45125-1
- language
- English
- LU publication?
- yes
- id
- aa4db098-f72d-47f1-a871-bd7aded86851
- date added to LUP
- 2024-02-14 08:24:17
- date last changed
- 2025-04-22 21:24:13
@article{aa4db098-f72d-47f1-a871-bd7aded86851, abstract = {{<p>Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.</p>}}, author = {{Papareddy, Praveen and Tapken, Ines and Kroh, Keshia and Varma Bhongir, Ravi Kiran and Rahman, Milladur and Baumgarten, Maria and Cim, Eda Irem and Györffy, Lilla and Smeds, Emanuel and Neumann, Ariane and Veerla, Srinivas and Olinder, Jon and Thorlacus, Henrik and Ryden, Cecilia and Bartakova, Eva and Holub, Michal and Herwald, Heiko}}, issn = {{2041-1723}}, keywords = {{Animals; Mice; NF-kappa B/metabolism; Extracellular Vesicles/metabolism; Biological Transport; Signal Transduction; Inflammation/pathology}}, language = {{eng}}, month = {{02}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{The role of extracellular vesicle fusion with target cells in triggering systemic inflammation}}, url = {{http://dx.doi.org/10.1038/s41467-024-45125-1}}, doi = {{10.1038/s41467-024-45125-1}}, volume = {{15}}, year = {{2024}}, }